Next Step in Management
The next step is to obtain a BNP or NT-proBNP level to evaluate for heart failure with preserved ejection fraction (HFpEF), followed by echocardiography if the BNP is elevated (≥100 pg/mL). 1, 2
Diagnostic Approach for Unexplained Dyspnea
Why BNP Testing is Critical Now
- BNP/NT-proBNP is the single most important next test when initial cardiac and pulmonary workup is unrevealing, with a BNP <100 pg/mL having 96-99% sensitivity for ruling out heart failure. 2
- A negative cardiac stress test does not exclude HFpEF, which is particularly common in middle-aged women and may present with normal systolic function but diastolic dysfunction. 3
- Clinical evaluation alone has high specificity (96%) but low sensitivity (59%) for cardiac causes, making biomarker testing essential. 3, 4
Second-Line Testing Based on BNP Results
If BNP is elevated (≥100 pg/mL):
- Proceed to echocardiography to assess for diastolic dysfunction, valvular disease (particularly mitral or aortic valve pathology), pulmonary hypertension, or pericardial disease. 3, 2
- Echocardiography should evaluate left ventricular ejection fraction, diastolic parameters, valve function, and right ventricular systolic pressure. 3
If BNP is normal (<100 pg/mL):
- Consider cardiopulmonary exercise testing (CPET) to identify exercise-induced limitations, deconditioning, exercise-induced bronchoconstriction, or exercise-induced arterial hypoxemia. 3, 1
- CPET can distinguish between cardiac, pulmonary, and deconditioning causes when resting tests are normal. 3
Additional Considerations for This Patient Population
- Exercise-induced bronchoconstriction (EIB) may not be detected on resting pulmonary function tests and requires exercise challenge or bronchoprovocation testing. 3
- Obesity-related dyspnea should be considered, as it causes increased oxygen cost of breathing without bronchoconstriction, particularly in women. 3
- Deconditioning is a common cause of exertional dyspnea in patients with normal resting cardiac and pulmonary function. 3
When to Refer to Specialists
- Refer to cardiology if echocardiography reveals valvular disease requiring intervention, HFpEF, or if cardiac etiology remains suspected despite negative initial testing. 3, 2
- Refer to pulmonology for consideration of interstitial lung disease (which may have normal spirometry), pulmonary vascular disease, or if CPET suggests pulmonary limitation. 3, 1
Common Pitfalls to Avoid
- Do not assume a negative stress test excludes all cardiac causes—it primarily rules out obstructive coronary disease but not HFpEF, valvular disease, or pulmonary hypertension. 3
- Do not overlook multiple concurrent causes—approximately one-third of patients with chronic dyspnea have multifactorial etiologies. 5, 6
- Do not delay evaluation of unexplained dyspnea—it is associated with increased all-cause mortality and may represent early manifestations of serious disease. 3, 6
If All Testing Remains Negative
- Consider CT chest to evaluate for interstitial lung disease, pulmonary vascular abnormalities, or subtle parenchymal disease not visible on chest radiography. 3, 4
- Evaluate for anemia, thyroid dysfunction, or metabolic acidosis if not already done. 4, 5
- Consider psychiatric causes (anxiety, panic disorder) only after thorough organic workup is completed. 7, 8